Understanding how the phenotype of an organism is produced by its genotype and environment is fundamental to modern biomedicine. Cellular biochemistry forms the best-characterized complex biochemical system available, and provides a unique opportunity to better understand the structure-function relationships that produce phenotypes. Understood mathematically, cells are a biochemical network whose topology, function, and possible behaviors are only still only dimly understood. Our previous work has resulted in the development of several databases (END, BND, Klotho) and software systems (The Agora, Glossa) to provide, accumulate, and use data on biochemical networks by users worldwide. In this application for competitive renewal, we propose to embark on a systematic study of structure-function relationships in biochemical networks, focusing on the discovery of patterns of biochemical function --- functional motives. We will identify these motives and their distribution over all enzymatic reactions by comparing changes in reactants' structures and enzymes' specificities, rather than just examine keywords. This systematic examination will allow us to determine, at much greater resolution than ever before, what functions each molecule and reaction have. To do this we must significantly extend the functionalities of our current systems in three major ways. First, we will add significant new data on the structure of small molecules of biochemical interest, enzymatic reactions, the mechanisms of gene expression, and dementia. Second, we will further develop and test methods that produce semantic interoperability among independent, disparate databases. Third, we will develop algorithms to detect and catalogue patterns of biochemical function among thousands of reactions and molecules; to more speedily enumerate paths among molecules and subnets in the biochemical network; to determine the extent of convergent evolution among enzymes; to trace atoms through a sequence of reactions such as a metabolic pathway; and to suggest novel biochemical reactions. We will use these capabilities to define and search for functional motives among enzymatic reactions, testing their correlation with network topology and dynamics, and to estimate the extent to which functional similarities arise from convergent evolution of enzymes.